Diabetes mellitus and Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): A wake-up call from Egypt

To the editor,

While the whole world started Coronavirus Disease 2019 (COVID-19) vaccine campaign aiming at ending the pandemic other areas of the world started to suffer from a devastating new complication of the disease. Increased cases of COVID-19 Associated Mucormycosis (CAM) has been noted [[1], [2], [3]]. We had observed this phenomenon in Egypt over the past few weeks similar to the situation in India.

All patients who had imaging findings of bone destruction and suspicion for fungal sinusitis following documented COVID-19 evaluated by authors from March 15th to May 15th^, 2021, were included. The patients’ demographic data, comorbidities, host risk factors, microbiologic data and management were collected.

The study included 21 patients evaluated in 11 different hospitals in metropolitan Cairo, Egypt (Patient characteristics in Table 1 ). Diabetes Mellitus was present in all patients on admission except two, 5/21 (23.8%) patients did not have prior history of diabetes and 3/21 (14.3%) presented with diabetic ketoacidosis, 10/21 (47.6%) had rhino-orbital disease, 5/21 (23.8%) had rhino-cerebral disease and one patient (4.7%) had pulmonary disease. 17/21 (81%) patients received amphotericin B either alone or in combination, 3 (14.3%) received itraconazole, and 2 (9.5%) received voriconazole. Mortality was 7/21 (33.3%), 5 of them (71.4%) had rhino-cerebral disease.

Table 1.

Characteristics of patients included in this report.

Age/Sex	Diabetes	Comorbidities	Presentation	Site	Treatment	Outcome	Surge	Microbiology	Notes
38/M	New onset	Sinusitis	- Nasal obstruction - Facial and orbital pain	Sinus	L-AmB then POS	Alive	Within 24h	Mucorales	Pathology proven mucormycosis
57/M	Yes	Hypertension	- Tooth pain and dysphagia - Headache	Sinus	L-AmB + POS then POS	Alive	Within 24h	No growth	Pathology proven mucormycosis Palatal perforation on admission
48/F	Yes	Morbid obesity	- Left eye ophthalmo-plegia and ptosis - Right orbital Apex syndrome	Rhino- orbital	L-AmB then POS	Alive	Within 48h	Mucorales and Aspergillus fumigatus	Pathology proven mucormycosis
54/M	Yes	Hypertension Atrial Fibrillation Ischemic cardiomyopathy Chronic Kidney disease	- Left facial palsy - Headache	Rhino- orbital	L-AmB plus POS	Alive	Not done	Pseudomonus aeroginosa	Pathology proven mucormycosis Palatal perforation on admission
55/M	Yes	Hypertension	Headache	Sinus	L-AmB	Alive	Not done	NA	Improved with medical treatment only
65/F	Yes	Hypertension Hypothyroidism Dyslipidemia	Respiratory Distress	Pulmonary	AmB plus POS	Alive	Not done	- Culture grew Rhizopus, Aspergillus flavus and Aspergillus fumigatus - Has associated CAPA and Polymicrobial Carbapenem Resistant acinetobacter and klebsiella pneumonia	- Received Tocilizumab
49/F	Yes with DKA	Ischemic heart disease	Right eye ophthalmoplegia and proptosis	Rhino- orbital	AmB	Alive	Not done	Not done	Lost to follow up
32/M	None	None	- Rt Periorbital oedma - Facial swelling and headache	Rhino, orbital	ITC	Alive	Within 24h	Culture grew only Acinetobacter Baumanni
56/M	Yes	Asthma Long Covid	- Left orbital edema - Ophthalmoplegia and vision loss	Rhino- orbital	AmB	Alive	Within 24h but later required orbital exentration	- Cultures grew only candida and aspergillus Sp	- Received Tocilizumab - Developed postoperative ischemic stroke
52/F	Yes	Ischemic heart disease Asthma	- Left orbital edema - Ophthalmoplegia with rapid deterioration of vision	Rhino- orbital	AmB then VRC	Alive	Within 48h but required orbital exentration	- Culture grew only Acinetobacter Baumanii	- Received Tocilizumab
61/M	Yes	Ischemic heart disease	- Left facial edema - Proptosis	Rhino- orbital	ITC	Alive	Within 72h	Negative cultures
39/M	New onset	None	- Left sided pansinusitis - Severe headache with retroorbital pain	Sinus	ITC	Alive	Within 72h	negative culture	Fungal mud with
45/F	None	None	- Left sided sinusitis - Diminution of vision with mild proptosis	Rhino- orbital	AmB	Alive	Within 48h	- Negative cultures	- Had periseptal and orbital abscess - Immediate postoperative improvement of vision
69/M	Yes	None	- Pansinusitis - Blackish discoloration of the palate - Malignant otitis externa	Sinus	VRC	Alive	24h	- Culture failed to grow mucor and only reported Aspergillus	- Received Tocilizumab - Had septal perforation - Required another endoscopic debridement after 2 weeks
60/F	Yes	Asthma Hypertension Ischemic stroke	Altered mental status	Rhino- orbital	L-AmB	Died (21D)	Not done	NA	L-AmB treatment interrupted due to AKI
68/M	Yes	Hypertension Ischemic cardiomyopathy Peripheral arterial disease Morbid obesity	Ptosis and ophthalmoplegia Blackish discoloration of face	Rhino- cerebral	L-AmB plus POS plus AFG	Died (13D)	Within 48h	- Culture grew Mucorales - Culture grew CR KP	- Confirmed by pathology - Course complicated by CR KP meningitis requiring intrathecal Colistin
65/F	New onset with DKA	Hypertension Ischemic heart disease	- Altered mental status - Blackish discoloration of face	Rhino- cerebral	L-AmB plus POS plus Anidulafungin	Died (11D)	5D	NA	CNS involvement with MCA occlusion on admission
72/M	Yes	Ischemic heart disease Chronic Kidney disease	- Bilateral diminution of vision	Rhino- cerebral	AmB then VRC	Died (25D)	Not done	Not done	- Patient had persistent positive COVID-19 swab that delayed surgery -Course complicated by massive ischemic stroke with central retinal artery occlusion
65/M	Yes	Hypertension	- Left eye swelling and pain - Left facial edema	Rhino- cerebral	L-AmB	Died (27 D)	Within 48h	- NA	- Received Tocilizumab - Left ICA occlusion with MCA infarction
36/M	New onset	None	Right eye swelling and proptosis	Rhino-orbital	L-AmB	Died (7D)	4 days	NA	Septic shock following surgery
44/M	New onset with DKA	Lumbar disk prolapse	Altered mental status Bilateral proptosis	Rhino-cerebral	AmB	Died (16 D)	Not done	Not done	Course complicated by cavernous sinus thrombosis and MCA occlusion

AFG: Anidulafungin; AKI: acute kidney injury; AmB: conventional amphotericin B; CAPA: Covid Associated Pulmonary Aspergillosis; CNS: central nervous system; CR KP: Carbapenem resistant Klebsiella pneumonia; D: day; DKA: diabetic ketoacidosis; F: female; GNB: Gram negative bacilli; ICA: internal carotid artery; ITC: itraconazole; L-AmB: liposomal amphotericin B; M: male; MCA: middle cerebral artery; POS: Posaconazole; VRC: voriconazole.

The aim of this study was to highlight the growing problem of CAM in Egypt and it was clear that younger patients had the best outcomes and older patients and patients with cerebral extension had the worse outcomes. Amphotericin B was the backbone of all our treatment regimens, diabetes was present in 90.5% of patients on admission. In the study of Singh et al. that included 101 CAM, most of them are from India, diabetes mellitus was present in 80% of cases and corticosteroid intake was administered by 76.3% of cases [2]. All our patients received corticosteroid therapy irrespective of clinical staging of COVID-19 which is largely driven by social media promoting high dose steroids. It was clear that patients who had early surgical debridement had the best outcome without organ loss and vision was preserved but there is always a selection bias as milder cases have better chances at surgery while critically ill patients either are too unstable for surgery or family defer procedure (Table 2 ).

Table 2.

Characteristics of the survived patients in comparison to the ones who died.

	Alive (14/21)	Deceased (7/21)
Sex	9 (64.3%) males 5 (35.7%) females	5 (71.4%) males 2 (28.6%) females
Age in years (mean ± SD)	50 ± 9.5	59.8 ± 12.9
Comorbidities and possible risk factors	12/14 (85.7%) Diabetes 14/14 (100%) corticosteroid intake 4/14 (28.6%) received Tocilizumab 4/14 (28.6%) Hypertension 4/14 (28.6%) Ischemic heart disease 1/14 (7.14%) Morbid obesity	7/7 (100%) Diabetes 7/7 (100%) corticosteroid intake 1/7 (14.2%) received Tocilizumab 4/7 (57.14%) Hypertension 3/7 (42.8%) Ischemic heart disease 1/7 (14.2%) Morbid obesity
Site	5/14 (35.7%) Sinus 8/14 (57.14%) Rhino-orbital 1/14 (7.14%) Pulmonary	2/7 (28.6%) Rhino-orbital 5/7 (71.4%) Rhino-cerebral
Treatment	1/14 (7.14) L-AmB 4/14 (28.6%) AmB 4/14 (28.6%) AmB and POS 3/14 (21.4%) ITC	3/7 (42.8%) L-AmB 2/7 (28.6%) L-AmB and POS 1/7 (14.3%) AmB
Surgical debridement	10/14 (%)	4/7 (57.14%)
Time of surgery	5/10 (50%) within 24 h 3/10 (30%) within 48 h 2/10 (20%) within 72 h	2/4 (50%) within 48 h ¼ (25%) after 4 days ¼ (25%) after 5 days

AmB: Conventional Amphotericin B; ITC: Itraconazole; L-AmB: Liposomal Amphotericin B; POS: Posaconazole.

CAM is a life-threatening condition that adds fuel to the fire and public health authorities should encourage following guidelines in COVID-19 and avoid non-evidence-based therapies.

Declaration of competing interest

The authors have no conflict of interest.